诱导线粒体DNA缩合克服耐药性的钌配合物抗肿瘤药物研究

linical anticancer drugs acting on DNA are limited by drug resistance, DNA damage repair, and apoptotic resistance, which are the two main reasons. To overcome this weakness, developing new forms of DNA interaction and inducing cancer cells to undergo nonapoptotic cell death is essential. Herein, a Ru(II) complex modified with a carbon chain and triphenylphosphine named RuDCT was synthesized as an mtDNA condensation inducer to trigger ferritinophagy. Briefly, RuDCT accumulates in mitochondria and inhibits mtDNA transcription by triggering DNA condensation. The RNA-seq analysis indicated that mitochondrial respiratory electron transport was disrupted. As a result, ATP consumption, ROS generation, and mitochondrial membrane potential loss occurred. Subsequently, RuDCT can efficiently overcome cisplatin resistance. To the best of our knowledge, RuDCT is the first case of a metal-based mtDNA condensation inducer as a chemotherapy anticancer agent.